WO1991008212A1

WO1991008212A1 - Mono-bino and di-bino oxodiaminodicyclophosphazene derivatives

Info

Publication number: WO1991008212A1
Application number: PCT/FR1990/000837
Authority: WO
Inventors: Jean-François Labarre; Pierre Castera; Jean-Paul Faucher; Marcel Graffeuil; François Sournies
Original assignee: Centre National De La Recherche Scientifique (Cnrs)
Priority date: 1989-11-24
Filing date: 1990-11-22
Publication date: 1991-06-13
Also published as: FR2655046A1; FR2655046B1

Abstract

An oxodiaminodicylophosphazene compound characterized in that its general formula is (I), wherein Z represents a chain of formula (II), wherein R and R' independently represent hydrogen or a C1-4? alkyl group, and n, m, p are independently integers between 1 and 10, where n may thereby formed, and R1? and R2? simultaneously represent chlorine or together form a chain of formula (II) as defined above, which is the same or different from the chain represented by Z. A method for preparing these compounds and their uses are also described.

Description

OXODIAMI NODICYCL OPHOSPHAZEN DERIVATIVES OF MO NO-BINO AND DI-BINO CONFIGURATION

The present invention was made at the Structure et Vie Laboratory - Faculty of Pharmacy at the Paul Sabatier University in Toulouse - Laboratory associated with the CNRS.

The present invention relates to oxodiaminodicyclophosphazenes derivatives of mono-BINO configuration (mono-bridged structures) and non-feminine di-BINO (di-bridged ethers-crown structures), processes for their preparation and their applications.

The action of biogenic polyamines (diaminopropane, putrescine, cadaverine, spermidine, spermine and homologs) on hexachloro-cyclotriphosphazene, N ₃ P ₃ Cl ₆ , leads in a stereospecific manner to unambiguous architectures whose nature depends on the polyamine used.

These architectures are made up of three basic configurations:

- the SPIRO loop in which two amino functions are covalently linked to the same phosphorus atom of the N ₃ P ₃ cycle,

the ANSA arch in which two amino functions are covalently linked to two different phosphorus atoms of the same N ₃ P ₃ ring, and,

- the BINO bridge in which two amino functions are covalently linked to two phosphorus atoms of two different N ₃ P ₃ rings.

The solubility in organic solvents of these three types of structure depends drastically on the presence or not of SPIRO loops in their molecular architecture. The presence of such loops provides the product with very high solubility while the presence of BINO bridges alone makes the solubility of the compound practically zero.

It is to overcome this difficulty that the inventors had the idea of reacting on N ₃ P ₃ Cl ₆ no longer purely hydrocarbon diamines but oxodiamines. It is known in fact that the introduction of oxygen atoms into the methylene chains of hydrocarbon diamines leads very generally to finished products much more soluble in the usual organic solvents than their non-oxygenated counterparts.

The present invention relates to oxodiamino-dicyclophosphazenes compounds, characterized in that they correspond to the general formula (I):

in which :

- Z represents a chain of formula (II)

-RN - [(CH ₂ ) _n -O] _p - (CH ₂ ) _m -NR'- (II) in which:. R and R ′ represent, independently of one another, a hydrogen or a C _1-4 alkyl group and,

. n, m, p are, independently of each other, integers from 1 to 10 with n possibly having different values in the alkoxy chain formed and,

- R ₁ and R ₂ simultaneously represent chlorine or together form a chain of formula (II), as defined above, identical or different from that represented by Z.

More particularly, the present invention relates to the compounds of formula (I) in which R ₁ and R ₂ form together and / or Z represents, independently of one another, a chain of formula (II), represented by one of the following structures:

-HN- (CH ₂ ) _n -O- (CH ₂ ) _m -NH- with m and n between 2 and 7 and preferably equal to 2;

-HN- (CH ₂ ) _n -O- (CH ₂ ) _n , -O- (CH ₂ ) _m -NH- with m, n and n 'between 2 and 7 and preferably equal to 2, 3 or 4 The compounds then have the name MACRO.

-HN- (CH ₂ ) _n -O- (CH ₂ ) _n , -O- (CH ₂ ) _{n "} -O- (CH ₂ ) _m -NH- with n, n ', n" and m between 2 and 7 and preferably being equal to 2 or

3. The compounds then have the name MEGA.

-HN- (C ₃ H ₆ O) _p -C ₃ H ₆ -NH- or -HN- (C ₂ H ₄ O) _p -C ₂ H ₄ -NH- with p equal to 4, 5 or more. In this case, the compounds are called GIGA.

The strings can also be numbered according to their structure in the form mOnOm. For example, the chain

Z = -HN- (CH ₂ ) ₃ -O- (CH ₂ ) ₂ -O- (CH ₂ ) ₃ -NH- will be noted (30203).

The invention also relates to processes for the preparation of the compounds of formula (I).

The oxodiaminodicyclophosphazenes derivatives according to the invention are obtained by reacting hexachlorocyclotriphosphazene N ₃ P ₃ Cl ₆ or a compound of formula (I) mono-BINO with at least one compound of formula (III):

[(CH ₂ ) _n - O] _p - (CH ₂ ) _{m (III)}

in which :

R and R ′ represent, independently of one another, a hydrogen or a C _1-4 alkyl group and,

n, m, p are, independently of each other, an integer from 1 to 1 0 with n possibly having different values in the alkoxy chain formed.

The derivatives of formula (III) are grafted onto N ₃ P ₃ Cl ₆ in so-called mono-BINO or di-BINO configurations which can be obtained in a stereoselective and / or stereospecific manner by varying the experimental conditions, c that is to say the nature of the solvent, the stoichiometry of the reaction and the order of introduction of the reactants. Thus, to prepare the compounds of formula (I) mono-BINO, the oxodiamine of formula (III) is added to N ₃ P ₃ Cl ₆ , preferably in a stoichiometry (1: 2), in a two-phase reaction medium Et ₂ O - water saturated with Na ₂ CO ₃ . (In the stoichiometries cited in this document, the quantity of the oxodiamine derivative is designated by the first digit). The role of the aqueous solution is to trap the hydrochloric acid formed during the reaction.

As for the compounds of formula (I) di-BINO, they can also be obtained from N ₃ P ₃ Cl ₆ and in the same biphasic reaction medium provided that they work with at least one equivalent of compound of formula (III). The reactions are then only stereoselective.

A second synthesis process, this time stereospecific, consists in preparing the compounds of formula (I) di-BINO from the compounds of formula (I) mono-BINO by adding at least one equivalent of the suitable oxodiamine. In ethyl ether and at the interface of a saturated aqueous solution of Na ₂ CO ₃ , stoichiometry is used (1: 1) while in acetonitrile or propanol, stoichiometry is preferred (2: 1). This second method also has the advantage of allowing the synthesis of di-BINO derivatives which are asymmetrical, that is to say which contain different oxodiamino bridges.

According to each of these methods, the desired compound of formula (I) is isolated from the reaction medium by decantation of the organic phase, drying of the latter with a dehydrating salt such as Na ₂ SO ₄ , evaporation of the solvent and elimination of N ₃ P ₃ CI ₆ unreacted

(when the reaction is carried out according to the first process). The final crude product is then purified by chromatography on silica in the case of mono-BINO compounds or by fractional crystallization for di-BINO compounds. The compounds of formula (I) are obtained with a yield which depends on the oxodiamine used but which can reach 90 ° 0.

These methods will be more precisely described in the examples.

The present invention also relates to the applications of these compounds of formula (I) obtained according to the invention. The X-ray structure of the compounds of formula (I) di-BINO highlights the accessibility of the coordination sites of the macrocycle present in the architecture with respect to a hard "acid" (metal or metalloid) or soft in the sense of PEARSON. It is thus possible to envisage exotic properties for these "encrypted" architectures. Intra-molecular complexation can be done by oxygen atoms

("hard" bases) and / or by the nitrogen atoms sp ("soft" bases) of the mono-BINO and di-BINO structures and this in a way which depends on the size of the macrocyclic cavity. We can thus selectively compress this or that cation in a complex mixture, with applications for the purification of metals with high added value for example. The complexed cations may be chosen from Lithium, Potassium,

Sodium, Magnesium or Calcium. As for the complexed metal cation, it will preferably be chosen from Bismuth, Yttrium, Copper, Cobalt, Titanium, Aluminum, Europium, Technetium, Gadolinium, Platinum, Palladium or Uranium. Similarly, inter-molecular complexation can also be achieved by the same coordination sites but with much more extensive possibilities as to the size of the metals that can be envisaged. The polydentate structures of the present invention can then give complexes of the "clusters" type usable in heterogeneous or homogeneous catalysis.

It is also possible to envisage the complexation of isotopes used in imaging and consequently the application of the complexes thus obtained for the localization in imaging of cancer cells.

The compounds according to the present invention can also be used in super-selective molecular membranes, in ionic conductors, in ion exchange resins or also in electromix systems.

Finally, they are also useful as chlorinated precursors of immunomodulatory anti-tumor drugs.

The examples and figures presented below without implied limitation will make it possible to highlight other advantages and characteristics of the present invention. Figures 1 to 4 show different views of the compound N ₃ P ₃ Cl ₄ [HN- (CH ₂ ) ₃ -O- (CH ₂ ) ₂ -O- (CH ₂ ) ₃ -NH] ₂ Cl ₄ P ₃ N ₃ (example 3 compound F)

EXAMPLE 1:

General method for the preparation of mono-MACRO-BINO compounds

N ₃ P ₃ Cl ₅ [HN- (CH ₂ ) _n -O- (CH ₂ ) _n , -O- (CH ₂ ) _m -NH] Cl ₅ P ₃ N ₃

(n = m = n '= 2: A, n = m = 3 and n' = 2: B and n = m = 3 and n '= 4: C):

Case of compound A:

2.13 g (14.4 mmol) of dioxodiamine 20202 dissolved in 200 ml of ethyl ether are added dropwise (addition time: 2 h) and with magnetic stirring to a solution of 10 g (28, 8 mmol) of N ₃ P ₃ CI ₆ in 300 ml of the same solvent at the interface of 50 ml of a saturated aqueous solution of Na ₂ CO ₃ . The reaction is stopped after 24 h. The organic phase is dried over Na ₂ SO ₄ and then evaporated under vacuum at 25 ° C. The crude product (9.65 g, yield 87%) is in the form of a whitish oil which is treated with n-heptane to remove the unreacted N ₃ P ₃ Cl ₆ . The final product (9.35 g) is a white micro-crystalline powder with a melting point of 80 ° C.

This procedure can be directly transposed to the preparation of compounds B (M = 84 ° C) and C (M = 88 ° C).

^{3 1} P NMR spectra, recorded at 81.015 MHz (BRUKER AC 200, in CDCl ₃ , with H ₃ PO ₄ 85% as reference) reveal a tripiet

(PClNH) centered on 19.10 (A), 18.38 (B) and 18.78 (C) ppm and a doublet (PCl ₂ ) centered on 21.48 (A), 21.32 (B) and 21 , 70 (C) ppm, ² J _PP = 47.5 (A), 46.7 (B) and 46.6 (C) Hz.

DCI mass spectrometry (NERMAG R 1010-H spectrometer) reveals the molecular peaks [MH ⁺ ] at the expected values [m / z 771

(A), 799 (B) and 826 (C)] with an isotopic distribution corresponding to the presence of 10 chlorine atoms in the molecule. The presence of the peak [M.NH ₄ ⁺ ] at m / z 788 (A), 816 (B) and 843 (C) is also observed in the three spectra. EXAMPLE 2:

Preparation of the mono-MEGA-BINO compound

N ₃ P ₃ Cl ₅ [HN- (CH ₂ ) ₃ -O- (CH ₂ ) ₂ -O- (CH ₂ ) ₂ -O- (CH ₂ ) ₃ -NH] Cl ₅ P ₃ N ₃ : D

3.16 g (14.4 mmol) of dioxodiamine 3020203 in 200 ml of ethyl ether are added dropwise (boiling time: 2 h) and with magnetic stirring to a solution of 10 g (28.8 mmol ) of N ₃ P ₃ Cl ₆ in 800 ml of the same solvent at the interface of an aqueous solution of 200 ml of water saturated with Na ₂ CO ₃ (surface of the interface of the order of 1 10 cm ² ). The reaction is stopped after 5 days. The organic phase is dried over Na ₂ SO ₄ and then evaporated under vacuum at 25 ° C. The crude product is a colorless oil which remains as such even after two successive chromatographies on a silica column with the ternary mixture of ethyl acetate / n-heptane / dichloromethane (6: 3: 1) as eluent (yield: 50% ).

The ^{3 1} P NMR spectrum, recorded at 81.015 MHz (BRUKER AC 200, in CDCl ₃ , with H ₃ PO ₄ 85% as reference) reveals a triplet

(PClNH) centered on 18.30 ppm and a doublet (PCI ₂ ) centered on 21, 35 ppm,

² J _PP = 46.5 Hz.

DCI mass spectrometry (NERMAG R spectrometer

1010-H) reveals the molecular peak [MH ⁺ ] at m / z 843, with an isotopic distribution corresponding to the presence of 10 chlorine atoms in the molecule. We also observe in the spectrum the presence of the peak [M.NH ₄ ⁺ ] at m / z 860.

EXAMPLE 3:

Preparation of di-MACRO-BINO compounds

N ₃ P ₃ Cl ₄ [HN- (CH ₂ ) _n -O- (CH ₂ ) _n , -O- (CH ₂ ) _m -NH] ₂ Cl ₄ P ₃ N ₃

non-feminine with n = m = n '= 2: E, n = m = 3 and n' = 2: F and n = m = 3 and n '= 4: G Case of compound E:

6.38 g (43.1 mmol) of oxodiamine 20202 dissolved in 250 ml of ethyl ether are added dropwise (addition time: 4 h) with magnetic stirring to a solution of 15 g (43.1 mmol ) of N ₃ P ₃ Cl ₆ in 1200 ml of the same solvent at the interface of 200 ml of a saturated aqueous solution of Na ₂ CO ₃ . The reaction is stopped after 24 h. The organic phase is dried over Na ₂ SO ₄ and then evaporated under vacuum at 25 ° C. The crude product thus obtained (13.7 g, yield: 76%) is a white powder which is crystallized from the dichloromethane / petroleum ether mixture.

(35-60 ° C) (3: 7) (Melting point: 85 ° C).

The ^{3 1} P NMR spectrum, recorded at 81.015 MHz (BRUKER AC 200, in CDCl ₃ , with H ₃ PO ₄ 85% as reference) reveals a triplet (PCI ₂ ) centered on 18.98 ppm and a doublet (PClNH) centered on 21.42 ppm, ² J _PP = 46.7 Hz.

This procedure can be directly extrapolated to the preparation of compounds F and G. The ³¹ P NMR parameters of these two homologs are as follows: (PCl ₂ ) = 20.63 (F) and 21.78 (G) ppm and

(PClNH) = 22.48 (F) and 21.78 (G) ppm, ² J _PP = 48.0 Hz for (F) (not measurable at 81.015 MHz for G).

DCI mass spectrometry (NERMAG R spectrometer

1010-H) reveals the molecular peaks [MH ⁺ ] at the expected values [m / z 843

(E), 899 (F) and 955 (G)] with an isotopic distribution corresponding to the presence of 8 chlorine atoms in the molecule. We do not observe here the presence of the peak [M.NH ₄ ⁺ ] at m / z 860 (E), 916 (F) and 972 (G).

The X-ray structure of compound (F) has been determined

(ENRAF-NONIUS CAD4 diffractometer). This compound crystallizes in the triclinical system, space group P1 bar, a = 9.019 (6), b = 9.224 (5), c =

1 1.542 (8) Å, α = 94.87 (4), β = 95.97 (4), γ = 99.68 (3) °, V = 936.5 (1) Å ³ , D _X = 1.599 (1) Mg m ^-3 , D _mes = 1.60 Mg m ^-3 (floating crystal method), R =

0.049 for 2862 unique reflections and 199 variables. The structure develops a 30-link macrocycle which can be likened to a crown-30 ether. Figures 1 to 4 bring together two views of the isolated molecule from the usual angles as well as two views of molecular packing. EXAMPLE 4:

Preparation of the di-MACRO-BINO compound

N ₃ P ₃ Cl ₄ [HN- (CH ₂ ) _m -O- (CH ₂ ) _n , -O- (CH ₂ ) _m -NH]

[HN- (CH ₂ ) _n -O- (CH ₂ ) _{n "} O- (CH ₂ ) _n -NH] CI ₄ P ₃ N ₃

non-asymmetric twin with m = 2, n '= 2 and n = 3, n "= 2: H

2 g (2.6 mmol) of (A) dissolved in 150 ml of acetonitrile are added dropwise (addition time: 4 h) and with magnetic stirring to a solution of 0.92 g (5.2 mmol) of oxodiamine (30203) in 350 ml of the same solvent. The reaction is stopped after 24 h.

After filtration of the hydrochloride, the clear solution is evaporated under vacuum at 25 ° C. The crude product is in the form of a pale yellow oil

(1.8 g, yield: 80%).

The ³¹ P NMR spectrum, recorded at 81.015 MHz (BRUKER AC

200, in CDCl ₃ , with H ₃ PO ₄ 85% as reference) reveals a triplet

(PCl ₂ ) at 18.99 ppm and a doublet (PClNH) at 21.38 ppm, ² J _PP = 46.9 Hz.

We therefore see that the ABC system expected in ³¹ P NMR for the compound

H (in which the two phosphorus atoms carrying the BINO bridges are a priori different) is reduced to a "false" system A ₂ B at 81.015 MHz whose chemical displacements are practically identical to those of the symmetrical compound E. Mass spectrometry DCI (NERMAG R spectrometer

1010-H) confirms, however, that it is indeed the expected asymmetric derivative since the molecular peak [MH ⁺ ] is observed at m / z 870 (molecular mass with ³⁵ Cl = 869.94), while the molecular masses of di-MACRO-BINO

(2O2O2) (E) and di-MACRO-BINO (3O2O3) (F) are respectively equal to

841.82 and 897.88.

EXAMPLE 5:

Preparation of the non-twin di-MEGA-BINO compound

N ₃ P ₃ Cl ₄ [HN- (CH ₂ ) ₃ -O- (CH ₂ ) ₂ -O- (CH ₂ ) ₂ -O- (CH ₂ ) ₃ -NH] ₂ Cl ₄ P ₃ N ₃ : J 1) Synthesis from N ₃ P ₃ Cl ₆ :

7.13 g (3.23 mmol) of the oxodiamine (3020203) dissolved in 200 ml of ethyl ether are added dropwise (addition time: 3 h) with strong magnetic stirring at 7.5 g ( 2.15 mmol) of

N ₃ P ₃ CI ₆ dissolved in 600 ml of the same solvent at the interface of 100 ml of a saturated aqueous solution of Na ₂ CO ₃ . The reaction is stopped after 24 h. The organic phase is dried over Na ₂ SO ₄ and evaporated under vacuum at

25 ° C. The crude product (4.70 g, yield: 38%) is a colorless oil which is chromatographed on a silica column with the acetonitrile / toluene mixture (7: 3) as eluent. The final product is in the form of deliquescent micro-crystals whose melting point has been impossible to measure.

The ³¹ P NMR spectrum, recorded at 81.015 MHz (BRUKER AC 200, in CDCl ₃ , with H ₃ PO ₄ 85% as reference) was to reveal an A ₂ B system similar to those observed for the compounds E, F and G. in reality, the spectrum is reduced to a "false" singlet at 21.60 ppm, which made it impossible to measure the coupling constant ² J _PP . The DCI mass spectrum (NERMAG R 1010-H spectrometer) gives the molecular ion [MH ⁺ ] at m / z 987 (molecular mass of J with ³⁵ Cl = 986) with a distribution of satellites which corresponds well to the presence of eight chlorine atoms in the molecule (maximum peak at MH ⁺ + 4 mass units).

2) Synthesis from D:

0.9 g (4.09 mmol) of oxodiamine (3O2O2O3) in 200 ml of ethyl ether are added dropwise over 4 hours with magnetic stirring to a solution of 3.45 g (4.09 mmol) of D in 600 ml of the same solvent at the interface of an aqueous solution of 50 ml of water saturated with Na ₂ CO ₃ . The reaction is stopped after 4 days. The organic phase is dried over Na ₂ SO ₄ and then evaporated under vacuum at 25 ° C. the crude product is a colorless oil (yield 70%). EXAMPLE 6

Preparation of the mono-BINO compound

N ₃ P ₃ Cl ₅ [HN- (CH ₂ ) _m -O- (CH ₂ ) _n -NH] Cl ₅ P ₃ N ₃ with m = n = 2: K

1.77 g (10 mmol) of dioxodiamine hydrochloride 2O2 (ALDRICH n ° 17609-5) and 6.95 g (20 mmol) of N ₃ P ₃ Cl ₆ are introduced into a 1 liter flask containing 250 ml of ethyl ether at the interface of an aqueous solution of 50 ml of water saturated with Na ₂ CO ₃ . The mixture is placed under magnetic stirring for 48 h at room temperature, the organic phase is then extracted, dried over Na ₂ SO ₄ and then evaporated in vacuo at 25 ° C. The crude product is a whitish oil which is treated with n-heptane, which dissolves the unreacted N ₃ P ₃ Cl ₆ . The insoluble part (title product) is a white powder (4.50 g, yield 62%), melting point 85 ° C.

The ^{3 1} P NMR spectrum, recorded at 81.015 MHz (BRUKER AC 200), in CDCl ₃ , with H ₃ PO ₄ as reference), reveals a triplet (PClNH) centered on 18.95 ppm and a doublet (PCl ₂ ) centered on 21.43 ppm, ² J _pp = 47.4 Hz.

EXAMPLE 7:

Preparation of the di-BINO compound

N ₃ P ₃ Cl ₄ [HN- (CH ₂ ) _m -O- (CH ₂ ) _n -NH] ₂ Cl ₄ P ₃ N ₃

non-twin with m = n = 2: L

1.77 g (10 mmol) of dioxodiamine hydrochloride 2O2 (ALDRICH n ° 17609-5) and 3.48 g (10 mmol) of N ₃ P ₃ Cl ₆ are introduced into a 1 liter flask containing 250 ml of ethyl ether at the interface of a saturated aqueous solution of Na ₂ CO ₃ . The mixture is placed for 48 h with magnetic stirring at room temperature. The organic phase is then dried over Na ₂ SO ₄ and evaporated in vacuo at 25 ° C. The gross product present in the form of a whitish oil. The unreacted N ₃ P ₃ Cl ₆ is removed by a simple washing with n-heptane. 3.1 g (82% yield) of a white powder with a melting point of 89 ° C. are thus recovered.

The ³¹ P NMR spectrum, recorded at 81.015 MHz (BRUKER AC 200, in CDCl ₃ , with H ₃ PO ₄ as reference), reveals a triplet (PCl ₂ ) centered on 18.94 ppm and a doublet (PClNH) centered on 21 , 47 ppm, ² J _PP = 47.0 Hz.

Claims

1. Oxodiaminodicyclophosphazene compound, characterized in that it corresponds to the general formula (I):

(I)

in which :

- Z represents a chain of formula (II):

-RN - [(CH ₂ ) _n -O] _P - (CH ₂ ) _m -NR '(II) in which

. R and R 'represent, independently of one another, a hydrogen or a C _{1 - 4} alkyl group and,

- R ₁ and R ₂ simultaneously represent chlorine or together form a chain of formula (II) as defined above, which is identical or different from that represented by Z.

2. Compounds of formula (I) according to claim 1, characterized in that R ₁ and R ₂ form together and / or Z represents, independently of one another, a chain of formula (II) having one of the following structures:

-HN- (CH ₂ ) _n -O- (CH ₂ ) _{n '} -O- (CH ₂ ) _m -NH-,

with m, n and n 'between 2 and 7 and preferably equal to 2, 3 or 4; -HN- (CH ₂ ) _n -O- (CH ₂ ) _{n '} -O- (CH ₂ ) _{n "} -O- (CH ₂ ) _m -NH- with n, n', n" and m between 2 and 7 and preferably being equal to 2 or

3,

-HN- (C ₃ H ₆ O) _P -C ₃ H ₆ -NH- or -HN- (C ₂ H ₄ O) _P -C ₂ H ₄ -NH- with p equal to 4, 5 or more.

3. Process for the preparation of an oxodiaminodicyclophosphazene compound of formula I, according to claim 1 or 2, characterized in that a hexachlorocyclotriphosphazene compound N ₃ P ₃ Cl ₆ or a compound of formula is reacted in a suitable solvent (I) mono-BINO with at least one compound of formula (III):

(III)

[(CH ₂ ) _n - O] _p - (CH ₂ ) _m -

in which :

R and R ′ represent, independently of one another, hydrogen or a C _1-4 alkyl group and,

n, m, p are, independently of each other, an integer from 1 to 10 with n possibly having different values in the alkoxy chain formed.

4. Preparation process according to claim 3, characterized in that the compounds of formula (I) mono-BINO are obtained by adding in a stoichiometry (1: 2) a compound of formula (III) to the hexachlorocyclotriphosphazene compound N ₃ P ₃ Cl ₆ in ethyl ether at the interface of an aqueous solution saturated with Na ₂ CO ₃ .

5. Preparation process according to claim 3, characterized in that the compounds of formula (I) di-BINO are obtained by adding at least one equivalent of a compound of formula (III) to a hexachlorocyclotriphosphazene compound N ₃ P ₃ CI ₆ in ethyl ether at the interface of an aqueous solution saturated with Na ₂ CO ₃ .

6. Preparation process according to claim 3, characterized in that the compounds of formula (I) di-BINO are obtained by adding at least one equivalent of a compound of formula (III) to a compound of formula (I) mono -BINO.

7. Preparation process according to claim 6, characterized in that adding an equivalent of a compound of formula (III) to a compound of formula (I) mono-BINO in ethyl ether at the interface d '' a saturated aqueous solution of Na ₂ CO ₃ .

8. Preparation process according to claim 6, characterized in that two equivalents of a compound of formula (III) are added to a compound of formula (I) mono-BINO in acetonitrile or propanol-2.

9. Compounds according to one of claims 1 and 2, characterized in that they are intra-molecular or inter-molecular complexes or cryptates with cations and / or "acid" metals within the meaning of

PEARSON.

10. Compounds according to claim 9, characterized in that the intramolecular complexed cations can be chosen from Lithium, Potassium, Sodium, Magnesium or Calcium.

1 1. Compounds according to Claim 9, characterized in that the selectively complexed metal can be chosen from Bismuth, Yttrium, Copper, Cobalt, Titanium, Aluminum, Europium, Technetium, Gadolinium , Platinum, Palladium or Uranium.

12. Compounds according to one of claims 9, 1 0 or 1 1, characterized in that the cations and / or the complex metals are radioactive.

13. Application of the complexes obtained according to one of claims 9 to 12 in homogeneous or heterogeneous catalysis.

14. Application of the complexes obtained according to one of claims 9 to 12 in imaging.

15. Application of the complexes obtained according to claims 9 to 12 in super-conductive structures.

16. Application of the complexes obtained according to claims 9 to 12 in super-selective molecular membranes.

17. Application of the complexes obtained according to the claims

9 to 12 in ionic conductors.

18. Application of the complexes obtained according to claims 9 to 12 in ion exchange resins.

19. Application of the complexes obtained according to claims 9 to 12 in electromix systems.

20. As chlorinated precursors of immunomodulatory antitumor drugs, the compounds according to one of claims 1 and 2 and 9 to 12.